The need to initiate treatment for a postmenopausal woman with a
low bone mass should be based on that individual's fracture risk
over a finite period of time. Fracture assessment tools, such as the
recently introduced FRAXTM model, allows the clinician to estimate an
individual's absolute fracture risk over the next decade of their
life. Such estimates are particularly useful for younger postmenopausal
females with bone density values in the osteopenic range. Fracture risk
increases with age and is inversely related to bone mineral density
values. A history of previous fracture after the age of 45 and within 10
years of assessment increases subsequent fracture risk.

Bone loss in women increases significantly during the late
perimenopausal period and may reach more than 2% annually in the early
postmenopausal period, particularly in the more hormonally sensitive
lumbar spine (trabecular bone). Femoral (cortical) bone loss is more
linear and is influenced by aging and estrogen deprivation. Women who
enter menopause with a low bone mass are at increased risk for
osteoporosis and fractures in the decade after menopause. The most
common fracture that occurs in the first decade of menopause involves
the distal forearm and results from an increased incidence of falls
sustained by women during that period of time. Such fractures,
particularly in women with low bone mass, are likely a marker for women
at increased risk for subsequent fractures. A 50-year-old woman with a
normal bone density has a 10-year fracture risk of about 6%, a figure
that doubles for females of that age with bone density scores in the
osteoporotic range. Women who are at the onset of menopause with normal
bone density values have a low 10-year fracture risk. Over a lifetime,
postmenopausal bone loss averages about 1% a year. Such progressive
age-related bone loss increases fracture risk. In general, healthy women
with no fracture history are at low fracture risk during the first
decade of menopause, unless they enter the menopausal transition with a
relatively low bone mass. Attention should be paid to balance issues and
falls prevention for all postmenopausal women as part of a comprehensive
fracture reduction strategy.

The decision to initiate bone-strengthening medication for a
postmenopausal woman with a low bone mass should be based on that
individual's absolute fracture risk. Recently introduced fracture
assessment tools allow clinicians to provide patients with an estimate
of their fracture risk over a finite period of time. In defining such
fracture risks, it is important to be cognizant of population-based
fracture rates among postmenopausal women with normal bone density
scores in order to compare the increased risk to age-related normative
values. Fragility or osteoporotic fractures increase with age, as older
bones are more likely to be less dense and to exhibit microarchitectural
changes, such as microcracks that are associated with such fractures.
Many women undergo bone density testing at the time of the menopausal
transition and are concerned about their bone health and fracture risk.
Fortunately, there have been a series of clinical studies that have
reported on serial bone density tests and fracture rates during the
first decade of menopause, and this data allows us to understand rates
of bone loss and fracture rates in the younger postmenopausal
population. Such information also allows the clinician to identify those
women in the first decade of menopause who are at enough increased risk
to warrant starting bone-strengthening treatment. The data also helps us
to assure most women in their fifties that they do not need immediate
treatment, as their finite time-related fracture risk is low. Bone loss,
however, is progressive, and many such women will require active
treatment as they age beyond the first decade of menopause.

Peak Bone Mass and Bone Loss in the First Decade of Menopause

Women accrue their greatest amount of bone, or peak bone mass,
generally, between 20 to 25 years of age. This maximum of bone mass is
mainly under genetic control. Women with eating disorders, low body
weight with secondary amenorrhea, sedentary habits, and other lifestyle
factors may fail to reach their full genetic potential for bone growth
and have lower bone masses than their age-related peers. (1) About 15%
of women aged 30 to 40 will have bone density scores in the osteopenic
range and about 3% will have osteoporotic range scores, most commonly in
the lumbar spine. (2) Over a normal life span, untreated females will
lose, on average, about 35% of their cortical bone and 50% of their
trabecular bone. (3) On an individual basis, however, there is
considerable variation of bone loss rates, with some women experiencing
rapid bone loss and others little or no bone loss. Postmenopausal bone
loss is influenced by genetic and environmental factors, especially low
body mass index. (4,5) Postmenopausal bone loss is usually progressive,
although recent data suggests that 9% of older women have stable bone
densities and that this subset of women have fewer fractures and live
longer than their age-matched peers, with either expected or increased
rates of bone loss. (6) Understanding rates of bone loss and short-term
fracture risk is critical to defining when and if younger postmenopausal
females need to begin bone strengthening therapies.

Zhai and colleagues investigated the natural history of
postmenopausal bone loss among almost 1000 Caucasian females from
Chingford in the United Kingdom who had at least two bone density tests
over a 15-year period. They found that bone loss from the femoral neck
was linear over time and averaged 1.67% annually, while lumbar spine
bone loss was significantly greater during the early postmenopausal
years and then slowed with increasing age. (7) In the American
observational multi-site investigation, the Study of Women's Health
Across the Nation (SWAN), which involves females of different ethnic
groups, Finkelstein and coworkers detailed rates of bone loss from the
pre- or early perimenopause through the first few years of
postmenopause. Investigators found that bone density changed very little
during pre- or early perimenopause, but, instead, declined more
significantly during late perimenopause. Through the early
postmenopausal years, annual rates of bone loss averaged 1.8% to 2.3% in
the spine and 1.0% to 1.4% in the hip, with rates of bone loss being
faster among those in the lowest tertile of body weight. They also
determined that ethnic differences in rates of bone loss were largely
eliminated when differences in body weight were controlled. (8) A
prospective study of bone loss in menopausal Australian women, conducted
by Guthrie and associates, involved 224 females aged 46 to 59 years, who
each underwent two bone density studies, an average of 24 months apart.
The women who became menopausal during the study had more bone loss at
the hip and spine than those who had become menopausal several years
earlier (Table 1). The most significant bone loss was seen at both the
hip and lumbar spine in the months immediately following the final
menstrual period. (9)

Fracture Rates in the First Decade of Menopause

Fracture rates are inversely related to bone density scores and are
highest among women with osteoporosis. However, the greatest number of
fractures occurs in the numerically much larger group of women with
osteopenia. (10) It is estimated there are about 8 million
postmenopausal American women with osteoporosis and as many as
three-times that number with osteopenia. (11) Identifying those subjects
at increased short- and intermediate-term risk of fractures, who may
need immediate bone strengthening treatment, is important in order to
reduce the incidence of fractures in high risk younger postmenopausal
women. Conversely, women at lower fracture risk during the first decade
of menopause can be reassured that they do not require immediate
pharmacologic intervention. A 50-year-old Caucasian female has a greater
than 50% risk of sustaining a fracture during the remainder of her life
time. (12) In the first decade of menopause, the greatest number of
fractures involves the distal forearm, while hip and vertebral fractures
occur with increasing frequency in the later postmenopausal years (Table
2). (13) The 10-year probability of a 50-year-old woman with a normal
bone density sustaining a fracture is about 6%. (14) Recently, there
have been a number of studies that have reported on the incidence of
fractures and rates of bone loss in younger postmenopausal females, and
this data further defines fracture risks and fracture sites for this
population.

The Danish Osteoporosis Prevention Study included 872 women (50.7
[+ or -] 2.9 years of age), who were not taking hormone replacement
therapy during early menopause, and were prospectively followed for 10
years. The outcome measures of this study included a bone density-based
diagnosis of osteoporosis of the femoral neck or spine at 10 years and a
history of fracture during that decade, or either alone. There were 78
fractures (9% of the population) sustained during the 10 years, over 80%
of which involved the distal forearm. Those women who fractured had
normal but significantly lower bone density scores at study entry than
did the women who did not fracture. Women with study entry T scores of
greater than -1.4 of either the spine or femoral neck had less than a
10% risk of developing osteoporosis or sustaining a fracture during the
first decade of menopause. Thirty-eight percent of women who were
osteopenic at study entry progressed to the development of osteoporosis
at the end of the 10-year period. (15)

The National Osteoporosis Risk Assessment (NORA) study is an
American population-based study involving over 200,000 postmenopausal
females, almost 71,000 of whom were between 50 to 59 years of age at
study entry. NORA was designed to study the relationship between bone
mineral density (at a peripheral site) and fractures at 1 and 3 years
after study entry. About 5% of the younger women had a peripheral bone
mineral density in the osteoporotic range at study entry. The first-year
fracture rate among the younger postmenopausal women was about 1%. (16)
Women with a history of a previous wrist fracture after age 45 had
three-times the risk of sustaining a fracture than did women without
such a fracture history. (17) Women in the NORA study with self-reported
poor health and lower bone density scores at study entry were at
increased short-term fracture risk. (18)

Clinical Decisions in the First Decade of Menopause

Bone loss and fracture rates, both among postmenopausal women with
normal as well as lower bone mineral density scores, help frame the
absolute risk for fractures that women in the first decade of menopause
face. It is clear that the younger postmenopausal women with a history
of a prior fracture in the decade preceding menopause are at higher risk
than their aged-matched peers with no fracture history. The decision to
recommend bone-strengthening medication to all postmenopausal women
regardless of age should be based on their absolute fracture risk, and
this is particularly so in the younger women who are likely to be at
less risk for short and intermediate-term fracture risk. The World
Health Organization's FRAXTM assessment model provides 10-year
fracture risks based on a number of individual variables, including body
mass index, age, smoking and alcohol intake history, current use of
corticosteroids, parental hip fracture history, prior fracture history,
and hip bone density scores. The computer-generated program, which is
based on past data provided by a large number of international
population-based studies, estimates an individual's 10-year risk of
a hip and a major osteoporotic fracture.

For American women with an absolute risk exceeding 3% (hip) or 20%
(major), bone-strengthening treatment is suggested. Such fracture
assessment tools help women understand their risk in simple mathematical
terms and reassure both the clinician and patient that the decision to
treat or not to start treatment is rooted in a risk assessment. It is
important to emphasize that the 1 -year risk is always the lowest risk
period and that deferring the start of treatment for several years may
be prudent for those with borderline 10-year risk profiles. A healthy 51
-year-old postmenopausal, nonsmoking woman with no previous fracture and
a femoral neck T score of -2.2 would have an 8.5% 10-year risk of a
major osteoporotic fracture. This static measure does not include rates
of bone loss, which may confer additional, increased risk; such a
patient should be followed closely with serial bone density tests and
measures of bone turnover.

High levels of such markers may influence the decision to recommend
treatment, particularly if they are reflected by significant declines in
bone density. (19) It is also important to remember that the incidence
of fractures is directly related to an increase in the rates of falling
among women, which begins as early as perimenopause when estrogen levels
start to decline. (20)

Conclusions

The decision to initiate treatment in females during the first
decade of menopause should be based on absolute fracture risk over a
finite period of time and on the need to preserve or increase a low bone
mass. It is generally agreed that postmenopausal women with osteoporotic
T scores should be treated, but the type of drug and the length of time
it should be used will depend on an individual's risk factors,
particularly bone mineral density, prior fracture history, and general
health. Healthy, younger postmenopausal women with only minimal or
moderately decreased bone mass and no fracture history are unlikely to
need treatment during the first decade of menopause. A falls prevention
strategy, including balance training, should be part of a comprehensive
fracture reduction program, particularly for those individuals with a
history of falls and balance problems. It is important to emphasize the
need for adequate amounts of dietary and supplemental calcium and
vitamin D, as well as to encourage patients to engage in regular
weightbearing exercises as ways to help maintain healthy and strong
bones.

Disclosure Statement

The author has no financial or proprietary interest in the subject
matter or materials discussed, including, but not limited to,
employment, consultancies, stock ownership, honoraria, and paid expert
testimony.

Stephen Honig, M.D., M.Sc., is Clinical Associate Professor, New
York University School of Medicine, and Director of The Osteoporosis
Center, Division of Rheumatology, Department of Medicine, NYU Hospital
for Joint Diseases, NYU Langone Medical Center, New York, New York.